This invention relates to heterocyclic-substituted 2-quinolone compounds. These compounds are cardiac stimulants which in general selectively increase the force of myocardial contraction without producing significant increases in the heart rate. The compounds are useful in the curative or prophylactic treatment of cardiac conditions, in particular heart failure.
Substituted quinolone derivatives are known in the art and certain of these prior art compounds have been suggested for pharmaceutical use.
For example, Japanese Patent Application No. 79-73783 published June 13, 1979 discloses pyridine-substituted quinolone derivatives of the general formula: ##STR2## wherein R is a lower alkyl group or phenyl-alkyl group. These compounds are stated to be useful as anti-ulcer agents and hypertensive drugs, but there is no evidence of any inotropic activity.
United Kingdom Patent Application No. 2127402A, published Apr. 11, 1984, discloses certain carbostyril derivatives of the formula: ##STR3## wherein one of R, R.sup.1 and R.sup.2 is a substituted pyridyl group and the other two are hydrogen atoms or certain substituent groups. These compounds are stated to be useful in the prophylaxis or treatment of thromboses, as coronary vasodilators, as hypotensive agents and as phosphodiesterase inhibitors.
United Kingdom Patent Application No. 2086896A, published May 19, 1982, discloses carbostyril compounds of the formula: ##STR4## wherein each of R.sup.1, R.sup.2 and R.sup.3 is a hydrogen atom or an organic substituent. These compounds are stated to have cardiotonic activity.
U.S. Pat. No. 4,258,185 discloses certain pyridazinone compounds which include, inter alia, compounds of the formula: ##STR5## wherein each of R.sup.1, R.sup.2, R.sup.4 and R.sup.5 is a hydrogen atom or an organic substituent and R.sup.3 is a hydrogen atom or R.sup.3 and one of R.sup.4 and R.sup.5 together form a single bond. The compounds are stated to be therapeutically useful as antithrombotic and antihypertensive drugs.
It has now been found that certain substituted 2-quinolone compounds which differ structurally from the above prior art compounds are useful cardiac stimulants in the treatment of congestive heart failure.